Is SEC24D p.Ile112Val (c.334A>G) pathogenic?

SEC24D p.Ile112Val (c.334A>G) is classified Likely benign in SEC24D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-24). AlphaMissense: likely benign (0.051); Ultra-rare (popmax 0.0107%, afr); Associated with Inborn genetic diseases.

What condition is associated with SEC24D p.Ile112Val (c.334A>G)?

SEC24D p.Ile112Val (c.334A>G) is associated with Inborn genetic diseases (ClinVar).

How common is SEC24D p.Ile112Val (c.334A>G) in the general population?

SEC24D p.Ile112Val (c.334A>G) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about SEC24D p.Ile112Val (c.334A>G)?

AlphaMissense predicts likely benign (score 0.051) — an in-silico prediction, not a clinical call.

SEC24D p.Ile112Val

c.334A>G · VCV3439182

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.051 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.051	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -5.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.22	GERP -1
Regional constraint	o/e 0.89	unconstrained · MANE · 110 kb · p 0.00018 · regional, not allelic
Overall
CADD	2.393	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% African / African-American · 8/75,010 alleles

Filtering AF 0.00527% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00105% 17/1,613,852 alleles · ultra-rare exomes 15/1,461,596 · genomes 2/152,256 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,376
Remaining individualsnot grpmax-eligible	0.0064%	15,623
South Asian	0.0011%	91,060
European (non-Finnish)	0.000339%	294,969

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SEC24D
Protein: p.Ile112Val
Coding: c.334A>G
MANE Select: NM_014822
Type: single nucleotide variant
Location: chr4:118817327 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.21 · 6 PDB
Residue 112: the 'disordered' region

Full SEC24D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SEC24D c.1824+1G>T Likely pathogenic ★★ same condition
SEC24D p.Ala218Val Uncertain significance ★★ ⚠ same condition
SEC24D p.Ala570Val Uncertain significance ★★ ⚠ same condition
SEC24D p.Ala774Asp Uncertain significance ★★ ⚠ same condition
SEC24D p.Ala94Thr Uncertain significance ★★ ⚠ same condition
SEC24D p.Arg365Thr Uncertain significance ★★ ⚠ same condition
SEC24D p.Asp1018Asn Uncertain significance ★★ ⚠ same condition
SEC24D p.Asp429Tyr Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/sec24d-p-ile112val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown